There is accumulating evidence that psychoactive and abused drugs exert their action by modifying synaptic membrane receptors and interfere with transmission of neuronal impulses. Whether they act as neurotransmitters or antagonists, pre- or post-synaptically, or in an indirect manner, is still open to question. A number of abused drugs are known to affect the acetylcholine receptor (nicotine, phenylcyclidine, belladonna alkaloids and their sympathetic derivatives, and cocaine). We have demonstrated receptor inhibition in a neuronal cell line by nicotine, phenylcyclidine, and a psychoactive glycolate ester. In the case of the acetylcholine receptor there now exists the unique opportunity to measure the effect of psychoactive drugs on the molecular steps involved in receptor function in both neuronal cell lines and membrane vesicles. We have now measured distinct processes involved in regulating the acetylcholine receptor controlled fluxes of specific inorganic ions: (1) the rate of movement of specific inorganic ions through the cell membrane, (2) the rate with which the receptors are inactivated (desensitized) by compounds which interact with the receptors on the membrane, (3) the constant for the equilibrium between active and desensitized receptor, (4) the rates of ion fluxes mediated by the desensitized form, and (5) the rate with which the receptor recovers on removal of the perturbing drug. Some of these measurements were made with PC12 cells which contain receptors characteristic of sympathetic neurons, and we can make all the measurements with vesicles containing a muscle-type acetylcholine receptor. Eventually, we hope to use neuronal cell lines from rat and mouse brain. A quench flow method has been developed with a time resolution of 10 msec which can be used to measure the receptor-controlled fluxes of specific inorganic ions in vesicles and cultures of sympathetic neurons and cells without breaking the vesicles or cells. Optical methods will be used to monitor the effect of psychoactive drugs on receptor-controlled changes in the transmembrane voltages of these cells. Psychoactive abused drugs can interfere with neural transmission by interfering with any of the steps which we have identified in the regulation of receptor-controlled fluxes of inorganic ions through the cell membrane.